DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5 June 2026 has been entered.
Response to Amendment
Claims 1, 5-7, 12-14, 16, and 19-20 have been amended, and Claims 21-23 have been newly added as requested in the amendment filed on 5 June 2026. Following the amendment, claims 1-3, 5-10, 12-16, and 18-23 are pending in the instant application.
Claims 14-16 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-3, 5-10, 12, and 21-23 are under examination in the instant office action.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 28 May 2026 were filed after the mailing date of the Final mailed 03/09/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-10, 12, and 21-23 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 7 have been amended to recite wherein the at least one PAD protein comprises “(ii) PAD1 or a protein having more than 25 consecutive amino acids of a full-length PAD1 and PAD4 or an antigenic fragment thereof”. It is unclear if the requirement of having more than 25 residues applies to the antigenic fragment, or if this encompasses fragments less than 25 amino acids. Thus, the length requirement of the claim is unclear.
This affects the scope of all depending claims.
Claim Rejections - 35 USC § 103 (New, Necessitated by Amendment)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
As currently amended to add new limitations, Claims 1-3, 5-7, 10, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Auger et al., Arthritis Rheumatol. 2020 Apr 26;72(6):903–911.
On pages 9-10 of Remarks filed 5 June 2026, Applicant traverses the rejection based upon the Seaman et al. art of record. New limitations, however, have been added to the claims which warrants further search and consideration. The Seaman et al. reference has been replaced by Auger et al., which was necessitated by amendment.
As currently amended Claim 1 recites: A method comprising: (a) contacting a biological sample from a subject having or suspected of having RA (rheumatoid arthritis) with at least one peptidyl arginine deiminase (PAD) protein, and (b) detecting a presence of an autoantibody reactive with the at least one PAD protein, wherein the presence of the autoantibody is indicative of RA, severity of RA, or risk of developing RA; wherein the at least one PAD protein comprises (i) PAD 1 or a protein having more than 25 consecutive amino acids of a full-length PAD1 protein, or (ii) PAD 1 or a protein having more than 25 consecutive amino acids of a full-length PAD1 protein an antigenic fragment thereof and PAD4 or an antigenic fragment thereof. Thus, contrary to Applicant’s arguments, the claims do not specifically require 25 consecutive amino acids within PADI4, but reads upon any antigenic fragment from PADI4.
Regarding Claim 1, Auger et al. teach patients with RA had both antibodies and T cell responses to PAD4. T cell responses to PADI4 peptides are associated with RA and correlate with anti-PAD4 antibodies (Abstract, Results). Specifically, peptide 8 consisting of the sequence DPGVEVTLTMKAASGSTGDQ, and peptide 61 consisting of the sequence PGFPVINGRCCLEEKVCSLL (See Figure 4). Both of these peptides bind all 5 different HLA-DR alleles. Additionally, IgG anti- PAD4 antibodies were detected in 11 (27%) of 41 patients with RA versus 1 (4%) of 25 patients with PsA and 0 of 11 healthy controls (both P = 0.004 by Fisher’s exact test) (Figure 1). IgM antibodies to human PAD4 were detected in 14 (34%) of 41 patients with RA versus 3 (12%) of 25 patients with PsA and 0 of 11 healthy controls (both P = 0.01 by Fisher’s exact test) (Figure 1). Thus, the prior art teaches contacting a biological sample from a subject having or suspected of having RA (rheumatoid arthritis) with at least one peptidyl arginine deiminase (PAD) protein. The full length of PAD14 is covered by peptides (see Figure 4), but Applicant has not fully analyzed the entire epitope that the autoantibodies recognize beyond stating peptides 8 and 61 each comprising 20 amino acids, are recognized by autoantibodies.
The prior art teaches peptides covering the full-length of PADI4, each peptide consisting of 20 amino acids, which reads upon antigenic fragments of PAD4, as claimed. Applicant argues the 25 consecutive amino acids of a full-length PADI1 protein is the preferred embodiment, yet as stated the claims do not require this length of peptide for PADI4. The exact epitopes that are recognized by the anti-PADI4 autoantibodies are not sequenced by Auger et al and very well may be longer than 20 residues.
Lastly, while the prior art differs from the claimed invention only with respect to the preferred length of the epitope recognized by the autoantibody, the Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. MPEP 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the reference does not “teach away” because it does not fully sequence the epitope recognized by the autoantibodies. Furthermore, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because the specification states the antigenic fragment of PAD “includes more than 3, more than 5, more than 10, more than 15, more than 20, more than 25, more than 50, more than 75, more than 100, more than 125, more than 150, more than 200, more than 250, more than 300, more than 350, more than 400, more than 500, or more than 600 consecutive amino acids of a full-length PAD polypeptide” (paragraph [0072]). Therefore, the prior art reference renders obvious the method of the instant claims.
Regarding claim 2, Auger et al. state that “PAD4 may not be the only target of T cells capable of providing help to ACPA- secreting B cells…any protein capable of binding and citrullinating peptides can be as relevant as PAD4 for activating T cells that can facilitate the production of ACPAs by the same hapten–carrier mechanism. This includes, for instance, PAD2, a PAD4 isoform also expressed in the RA synovium, or bacterial PADs that are not homologous to eukaryotic PADs but still bind and citrullinate peptides” (pg. 910 paragraph bridging columns). Thus, the prior art explicitly suggests looking at other PAD proteins including PAD2 of the instant claims.
Regarding claim 3, the method of Auger et al. utilizes sera from patients to detect autoantibodies (see pg. 904, section titled Detection of anti-APAD4 antibodies).
Regarding claim 5, Auger et al. teach wherein the at least one PAD protein or antigenic fragment thereof is obtained by recombinant expression, wherein it teaches: “ Human PAD4 was produced in a baculovirus expression system (ProteoGenix) and purified” (pg. 904, section titled Proteins). Additionally, Auger et al. also produce peptides by synthesis wherein they disclose, “Peptides were synthesized using a solid-phase system (Neosystems) and purified (>70%). We synthesized 65 20-mer peptides, encompassing residues 1–663 of wild- type PAD4 (residues S55, A82, and A112, on locus NM_012387) and overlapping on 10 amino acids” (pg. 904, section titled Synthetic peptides of human PAD4).
Regarding claim 6, wherein the detecting comprises contacting the autoantibody bound to the at least one PAD protein or antigenic fragment thereof with a detection probe, wherein detecting using the detection probe comprises at least one of (i), (ii), or (iii) as follows, where:(i) the detection probe binds to the autoantibody;(ii) the detection probe comprises an antibody or functional fragment thereof; or (iii) the detection probe comprises a reporter tag, wherein the reporter tag comprises a label, a fluorescent label, a ligand, a particle, a nanoparticle or a combination comprising at least two of a label, a fluorescent label, a ligand, a particle, or a nanoparticle, wherein the label is selected from a fluorophore, an enzyme, a chemiluminescent moiety, a radioactive moiety, an organic dye, or a small molecule; wherein the fluorescent label is optionally phycoerytherin (PE); or wherein the ligand optionally comprises biotin. Specifically, Auger et al. teach: “Plates were coated with 0.5 μg of human PAD4 and blocked with 2% bovine serum albumin (BSA). Sera were diluted 1:100 and incubated on plates. After washing, peroxidase- conjugated anti-human IgG or IgM was added” which teaches the detection probe comprises a reporter tag. Auger et al. state: “Optical density (OD) was read at 405 nm”, which explicitly teaches fluorescent labeling that is read at a deep violet wavelength.
Regarding claim 7, as stated for claim 6 above, Auger et al. teach contacting a biological sample (sera of the reference) from a subject having or suspected of having RA (rheumatoid arthritis) with at least one peptidyl arginine deiminase (PAD) protein or fragment thereof (see Figure 4) and detecting a presence of an autoantibody reactive with the at least one PAD protein (see Figure 1). Specifically, Figure 1 demonstrates higher levels of anti-PAD4 IgG and IgM relative to psoriatic arthritis and healthy controls. Thus, indicating the presence of the autoantibody is indicative of RA disease.
Regarding claim 10, Auger et al. utilize sera from patients.
Regarding claim 12, as stated above, Auger et al. teach the at least one PAD protein or antigenic fragment thereof is obtained by chemical synthesis (pg. 904, section titled Synthetic peptides of human PAD4) or recombinant expression (pg. 904, section titled Proteins).
Regarding claim 13, the detection of autoantibodies comprises contacting the sera with PAD peptides (Figure 4) and a detection probe (secondary anti-human antibody) that produces a fluorescent OD at 405 nm.
Thus, the method of the invention is rendered obvious over the methods disclosed in the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-10, and 12-13 stand as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 70-75 of copending Application No. 19/184,462 (reference application) in view of Auger et al cited above.
On page 11 of Remarks filed 5 June 2026, Applicant argues that claims now recite PAD1 or a protein having more than 25 consecutive amino acids.
This is not persuasive because the claim still recites PAD4 or an antigenic fragment thereof, which is taught by the Auger et al. reference as outlined above. Furthermore, limitations of the reference claim are drawn to “detecting a presence of an autoantibody reactive with the at least one PAD protein” which is the generic form of the instant claims directed to PADI1 or PADI4. MPEP 2131.02 states, a generic claim cannot be allowed to an applicant if the prior art discloses a species falling within the claimed genus”. Thus, the species of the instant claims would anticipate the genus of the co-pending application. The rejection is maintained.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/STACEY N MACFARLANE/Examiner, Art Unit 1675
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